DESCRIPTION: (Applicant's Abstract) Large scale duplication, from chromosomal fragments to the entire genome, followed by mutation is considered a major force driving functional diversity in vertebrates. Isolated examples of duplicated regions support this theory, but a genome-wide study of mammalian gene duplication and subsequent functional diversification has not been attempted. A better understanding of the functional similarities between duplicated genes would greatly enhance the power of paralogous relationships in predicting gene function and understanding genetic disease. The candidate's long-term career goal is to establish an independent, research program in academia, using computational genomics to study the role of gene duplication in the evolution, structure and function of mammalian genomes. The specific goals of the current proposal constitute the first step in this program and will allow the candidate to demonstrate the feasibility of her interdisciplinary approach. They are (1) to construct a spatially ordered set of all discernible duplicated genes in the mouse and human genomes and to estimate the time of duplication for each; (2) to develop algorithms to identify the number of large scale duplications that took place and determine the sequence of rearrangements that subsequently fragmented them; (3) to determine, using probabilistic models of rearrangements, to what extent spatial organization of duplicated regions is preserved; and (4) to annotate the duplication data with functional data in preparation for studying the processes of functional differentiation following duplication.